The effects of a psychiatric clerkship on stigmatizing attitudes toward mental disorders as held by German medical students.

Background: According to the United Nations, access to medical care is a fundamental human right. However, there is widespread stigmatization of severe mental illnesses and this appears to seriously hamper the quality of healthcare in people with psychiatric co-morbidity. Thus, interventions that help reduce stigma among healthcare providers are urgently needed. Purpose: The objective of the current study was to investigate the effects of a psychiatric clerkship on stigmatizing attitudes toward mental disorders held by medical students. Methods: Between 2018 and 2019, a total of 256 third- and fourth-year students from Marburg University Medical School (Germany) completed two surveys-one before and one after a 2 week clerkship program that was designed to prioritize direct interaction with the patients. For measuring stigma, the questionnaires contained questions about students' attitudes toward psychiatry (ATP), including the Opening Minds Scale for Healthcare Providers (OMS-HC), Community Attitudes Toward the Mentally Ill (CAMI), and measurements according to the Stereotype-Content Model (SCM). We conducted pre-vs.-post comparisons using the Wilcoxon signed rank test with continuity correction or paired t-test and employed the Spearman method for correlational analysis. We considered p < 0.05 significant and adjusted all p-values reported here using the Benjamini-Hochberg procedure to account for family-wise error. Results: After the clerkship, a significantly reduced stigma was found, as assessed with ATP (mean p < 0.001), OMS-HC (sum and subscale "attitudes" p < 0.001; subscale "disclosure" p = 0.002), and both SCM subscales (p < 0.001). Moreover, we observed significant associations between stigma expression (e.g., OMS-HC sum) and the willingness of students to choose psychiatric residency after finishing medical school (before clerkship: p < 0.001; ρ = -0.35; change after clerkship: p = 0.004; ρ = -0.2). Conclusion: Our findings indicate that a psychiatric clerkship that involves students in direct interaction with patients may effectively reduce stigma. Therefore, we advocate the incorporation of components of direct interaction in medical education to combat stigma and unequal treatment, as this could improve outcomes in patients with severe mental illnesses.

Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma.

CDKN2A deletion is a common alteration in pleural mesothelioma (PM) and frequently associated with co-deletion of MTAP. Since the standard detection method for CDKN2A deletion and FISH analysis is relatively expensive, we here investigated the suitability of inexpensive p16 and MTAP IHC by comparing concordance between IHC and OncoScan CNV arrays on samples from 52 PM patients. Concordance was determined using Cohen's kappa statistics. Loss of CDKN2A was associated with co-deletion of MTAP in 71% of cases. CDKN2A-MTAP copy-number normal cases were also IHC positive in 93% of cases for p16 and 100% for MTAP, while homozygous deletion of CDKN2A-MTAP was always associated with negative IHC for both proteins. In cases with heterozygous CDKN2A-MTAP loss, IHC expression of p16 and MTAP was negative in 100% and 71%, respectively. MTAP and p16 IHC showed high sensitivity (MTAP 86.5%, p16 100%) and specificity (MTAP 100%, p16 93.3%) for the detection of any gene loss. Loss of MTAP expression occurred exclusively in conjunction with loss of p16 labeling. Both p16 and MTAP IHC showed high concordance with Oncoscan CNV arrays (kappa = 0.952, p < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.

Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns.

Aggregation of the RNA-binding protein TAR DNA-binding protein 43 (TDP-43) is the key neuropathological feature of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). In physiological conditions, TDP-43 is predominantly nuclear, forms oligomers, and is contained in biomolecular condensates assembled by liquid-liquid phase separation (LLPS). In disease, TDP-43 forms cytoplasmic or intranuclear inclusions. How TDP-43 transitions from physiological to pathological states remains poorly understood. Using a variety of cellular systems to express structure-based TDP-43 variants, including human neurons and cell lines with near-physiological expression levels, we show that oligomerization and RNA binding govern TDP-43 stability, splicing functionality, LLPS, and subcellular localization. Importantly, our data reveal that TDP-43 oligomerization is modulated by RNA binding. By mimicking the impaired proteasomal activity observed in ALS/FTLD patients, we found that monomeric TDP-43 forms inclusions in the cytoplasm, whereas its RNA binding-deficient counterpart aggregated in the nucleus. These differentially localized aggregates emerged via distinct pathways: LLPS-driven aggregation in the nucleus and aggresome-dependent inclusion formation in the cytoplasm. Therefore, our work unravels the origins of heterogeneous pathological species reminiscent of those occurring in TDP-43 proteinopathy patients.

Sources of PM2.5-Associated Health Risks in Europe and Corresponding Emission-Induced Changes During 2005-2015.

We present a newly developed approach to characterize the sources of fine particulate matter (PM2.5)-related premature deaths in Europe using the chemical transport model GEOS-Chem and its adjoint. The contributions of emissions from each individual country, species, and sector are quantified and mapped out at km scale. In 2015, total PM2.5-related premature death is estimated to be 449,813 (257,846-722,138) in Europe, 59.0% of which were contributed by domestic anthropogenic emissions. The anthropogenic emissions of nitrogen oxides, ammonia, and organic carbon contributed most to the PM2.5-related health damages, making up 29.6%, 23.2%, and 16.8%, respectively of all domestic anthropogenic contributions. Residential, agricultural, and ground transport emissions are calculated to be the largest three sectoral sources of PM2.5-related health risks, accounting for 23.5%, 23.0%, and 19.4%, respectively, of total anthropogenic contributions within Europe. After excluding the influence of extra-regional sources, we find eastern European countries suffered from more premature deaths than their emissions caused; in contrast, the emissions from some central and western European regions contributed premature deaths exceeding three times the number of deaths that occurred locally. During 2005-2015, the first decade of PM2.5 regulation in Europe, emission controls reduced PM2.5-related health damages in nearly all European countries, resulting in 63,538 (46,092-91,082) fewer PM2.5-related premature deaths. However, our calculation suggests that efforts to reduce air pollution from key sectors in some countries can be offset by the lag in control of emissions in others. International cooperation is therefore vitally important for tackling air pollution and reducing corresponding detrimental effects on public health.

Association of Interprofessional Discharge Planning Using an Electronic Health Record Tool With Hospital Length of Stay Among Patients with Multimorbidity: A Nonrandomized Controlled Trial.

Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial. Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity. Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022. Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning. Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals. Results: There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time. Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge. Trial Registration: isrctn.org Identifier: ISRCTN83274049.

Comprehensive Validation of Diagnostic Next-Generation Sequencing Panels for Acute Myeloid Leukemia Patients.

Next-generation sequencing has greatly advanced the molecular diagnostics of malignant hematological diseases and provides useful information for clinical decision making. Studies have shown that certain mutations are associated with prognosis and have a direct impact on treatment of affected patients. Therefore, reliable detection of pathogenic variants is critically important. Here, we compared four sequencing panels with different characteristics, from number of genes covered to technical aspects of library preparation and data analysis workflows, to find the panel with the best clinical utility for myeloid neoplasms with a special focus on acute myeloid leukemia. Using the Acrometrix Oncology Hotspot Control DNA and DNA from acute myeloid leukemia patients, panel performance was evaluated in terms of coverage, precision, recall, and reproducibility and different bioinformatics tools that can be used for the evaluation of any next-generation sequencing panel were tested. Taken together, our results support the reliability of the Acrometrix Oncology Hotspot Control to validate and compare sequencing panels for hematological diseases and show which panel-software combination (platform) has the best performance.

Attitudes towards refugees: Introducing a short three-dimensional scale.

Many researchers subscribe to the three-component conceptualization of attitudes, the idea that attitudes have cognitive, affective, and behavioural (intentional) components. Yet, these components are rarely considered simultaneously in scales, especially those measuring attitudes towards refugees. Moreover, it is debated how these components relate to one another. We present the development and validation of a six-item short-scale to measure attitudes towards refugees based on three surveys (Study 1: N = 330; Study 2a: N = 2,083; Study 2b: N = 2,174). We assessed the performance of this scale with respect to three rivalling attitude conceptualizations (one-factor, three-factor, and second-order factor model). We found that a three-factor or second-order factor conceptualization fitted best to the data. The scale had excellent psychometric properties. We hope that our work stimulates a wave of relevant research on attitudes towards refugees that applies this scale, and contributes to the debate on the conceptualization of attitudes in general.

Novel RGAG1-BCOR gene fusion revealed in a somatic soft tissue sarcoma with a long follow-up.

BCOR-rearranged sarcomas are rare and belong to the Ewing-like sarcomas (ELS). Their morphology and histopathological features make the diagnosis challenging. We present a case, initially diagnosed as an unusual extraskeletal myxoid chondrosarcoma (EMC). A 54-year-old male patient developed an asymptomatic swelling of the lower leg. Imaging showed a 9.5-cm large intramuscular soft tissue mass. Due to its morphological and immunohistochemical profile on biopsy, it was initially diagnosed as an EMC. The patient was treated by complete resection and adjuvant radiotherapy and remained free of tumor at 7 years follow-up. Using next-generation sequencing (NGS), we retrospectively identified RGAG1-BCOR gene fusion (confirmed by RT-PCR), which has not been described in somatic soft tissue tumors so far. This finding broadens the spectrum of partner genes in the BCOR-rearranged sarcomas in a tumor with a well-documented, long clinical follow-up.

Setting a diagnostic benchmark for tumor BRCA testing: detection of BRCA1 and BRCA2 large genomic rearrangements in FFPE tissue - A pilot study.

PARP inhibitors are used for treatment of tumors lacking function of the double-strand DNA break repair proteins BRCA1 or BRCA2 and are already approved for several cancer types. Thus, it is clinically crucial to determine germline as well as somatic BRCA1/2 mutations in those patients. The amplicon-based Oncomine BRCA1 and BRCA2 Assay is a test routinely used in diagnostics with FFPE specimens. The assay is validated for the detection of mutations, however, data on its performance in detecting large genomic rearrangements in FFPE tissue, is scarce. We cross-validated Oncomine BRCA1 and BRCA2 Assay in blood samples and/or FFPE tissue with multiplex ligation-dependent probe amplification (MLPA) for exon deletions and with OncoScan and an in-house hybridization-based target capture assay (MelArray) with a customized pipeline for the detection of loss of heterozygosity (LOH) and heterozygous versus complete gene loss. The Oncomine BRCA1 and BRCA2 Assay could detect both exon deletion and mono- and bi-allelic losses of the BRCA1/2 genes. We show that the therapeutically relevant large genomic rearrangements are reliably detected with the amplicon-based Oncomine BRCA1 and BRCA2 Assay in FFPE tumor tissue. Based on our data, we suggest tumor BRCA testing as standard diagnostic prescreening prior to germline BRCA testing.

Quantitative phase measurements of human cell nuclei using X-ray ptychography.

The human cell nucleus serves as an important organelle holding the genetic blueprint for life. In this work, X-ray ptychography was applied to assess the masses of human cell nuclei using its unique phase shift information. Measurements were carried out at the I13-1 beamline at the Diamond Light Source that has extremely large transverse coherence properties. The ptychographic diffractive imaging approach allowed imaging of large structures that gave quantitative measurements of the phase shift in 2D projections. In this paper a modified ptychography algorithm that improves the quality of the reconstruction for weak scattering samples is presented. The application of this approach to calculate the mass of several human nuclei is also demonstrated.

Nanofocusing with aberration-corrected rotationally parabolic refractive X-ray lenses. Corrigendum.

A correction in the paper by Seiboth et al. [(2018). J. Synchrotron Rad. 25, 108-115] is made.

Myoepithelial Carcinoma of Soft Tissue With an EWSR1-KLF15 Gene Fusion in an Infant.

Overall, neonatal cancer is uncommon. Because of its rarity and heterogeneity, diagnosis can be challenging. We report a unique case of a myoepithelial carcinoma in a 7 week old girl. Molecular diagnostic workup revealed a EWSR1-KLF15 gene fusion which was previously described in only six cases of myoepithelial tumors so far. All cases occurred in children and adolescents. To our knowledge, this is the first report of a congenital EWSR1-KLF15 fusion positive myoepithelial tumor in an infant.

Association of in-hospital multimorbidity with healthcare outcomes in Swiss medical inpatients.

IMPORTANCE: Multimorbidity poses a worldwide health- and socio-economic challenge, exacerbated by changing demographics. The association of multimorbidity with healthcare outcomes in hospitalised medical inpatients remains incompletely understood. OBJECTIVE: To examine the prevalence and burden of in-hospital multimorbidity over a 6-year time period and its association with in-hospital mortality, intensive care unit admission, length of hospital stay and readmission rates. DESIGN: This cross-sectional study analysed Swiss hospital discharge records from 1 January 2012 to 31 December 2017. SETTING: The study used population-based, administrative data from the Swiss Federal Statistical Office to investigate all adult medical cases in Switzerland. PARTICIPANTS: 2,220,000 population-based medical discharge records from 1,463,781 anonymised patients were included in the analysis. Multimorbidity was defined according to the World Health Organization as the presence of at least two chronic conditions. We applied the “Chronic Condition Indicator for the International Classification of Diseases (ICD-10-CM)”, which divides all ICD-10 codes into chronic and acute conditions, to define the number of chronic conditions. MAIN MEASURES: Time- and age-stratified prevalence of multimorbidity and its association with in-hospital mortality, ICU admission rate, length of stay, 30-day and 1-year all-cause readmission rates. RESULTS: Of the 2,220,000 cases, 51.3% were male with a mean age of 68.0 years (standard deviation 17.4). A total of 1,769,530 (79.7%) were multimorbid with a median of 4 (interquartile range 2–6) chronic conditions. The prevalence of multimorbidity increased by about 1.0% per year over the 6-year study period from 76.1% (2012) to 82.2% (2017). Multimorbidity was associated with higher odds of in-hospital mortality (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.28 to 1.34), ICU admission rate (OR 3.29, 95% CI 3.23 to 3.34), length of stay (+2.7 days, 95% CI 2.6 to 2.7), 30-day- (OR 1.92, 95% CI 1.89 to 1.94) and 1-year all-cause readmission rates (OR 1.70, 95% CI 1.68 to 1.71). The associations with in-hospital mortality and readmission were strongest in younger patients. CONCLUSIONS: Multimorbidity is highly prevalent in medical inpatients and has a relevant association with poor healthcare outcomes. Further investigation is needed to specify risk factors as well as to optimise the management of multimorbid patients to improve outcomes.

Alterations in BAP1 Are Associated with Cisplatin Resistance through Inhibition of Apoptosis in Malignant Pleural Mesothelioma.

PURPOSE: The clinical standard treatment for patients with malignant pleural mesothelioma (MPM) includes a cisplatin-based chemotherapy, leading to reduction of tumor size in only a minority of patients. Predicting response to chemotherapy in patients with MPM by using a genetic marker would, therefore, enable patient stratification. EXPERIMENTAL DESIGN: In this retrospective biomarker study, eligible patients had resectable MPM, measurable disease, and available primary MPM tissue. All patients underwent first-line treatment with cisplatin and pemetrexed, followed by surgery. Thorough molecular analysis was performed (whole-exome and targeted deep sequencing, and copy-number analyses), and also mechanistic in vitro data (viability assays, Western blots, and immunoprecipitation) using mesothelioma cell lines with and without siRNA-mediated BRCA1-associated protein 1 (BAP1) knockdown were provided. RESULTS: In a training cohort of patients with MPM (n = 28), mutations or deletions of BAP1 each predicted resistance to chemotherapy in patients with primary MPM. The negative predictive value of BAP1 loss in patients with MPM was confirmed by amplicon sequencing and copy-number array technology in an independent test cohort (n = 39). Preliminary mechanistic studies using siRNA-based knockdown of BAP1 in MPM cell culture models along with immunoprecipitation assays confirmed chemoresistance in vitro, possibly through inhibition of apoptosis and transcriptional regulation of the BAP1/HCF1/E2F1 axis. CONCLUSIONS: Alterations in BAP1 in MPM were a negative predictor for response to chemotherapy and could possibly be used as a companion biomarker for treatment decision.

The dynamic relationship between contact opportunities, positive and negative intergroup contact, and prejudice: A longitudinal investigation.

We investigated the dynamics of naturally increasing contact opportunities, frequencies of positive and negative intergroup contact experiences, and prejudice toward forced migrants, in 2 three-wave longitudinal studies (Study 1, N = 183, adult community sample; Study 2, N = 758, nation-wide adult probability sample) in Germany using latent growth curve and parallel process analyses. We examined (research question 1) whether prejudice increases or decreases with increased contact opportunities; (research question 2) whether the rate of change in prejudice is related to the rate of change of positive/negative contact; (research question 3) whether the trajectories of change in prejudice shift as a function of the histories of prior positive/negative contact; and (research question 4) whether the rate of change in positive/negative contact frequencies depends on prior prejudice levels. Across both studies, prejudice increased with increased contact opportunities, as did positive and negative contact frequencies (ad research question 1). Whereas changes in negative contact were significantly related to changes in prejudice in both studies, no such relationships emerged as significant for positive contact (ad research question 2). We did not find any supportive evidence for our research questions 3 and 4. Overall, our results demonstrate that increased contact opportunities can contribute to increases in prejudice. Moreover, they indicate that the trajectories of negative contact and prejudice may be more substantially intertwined than the trajectories of positive contact and prejudice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Convergent network effects along the axis of gene expression during prostate cancer progression.

BACKGROUND: Tumor-specific genomic aberrations are routinely determined by high-throughput genomic measurements. It remains unclear how complex genome alterations affect molecular networks through changing protein levels and consequently biochemical states of tumor tissues. RESULTS: Here, we investigate the propagation of genomic effects along the axis of gene expression during prostate cancer progression. We quantify genomic, transcriptomic, and proteomic alterations based on 105 prostate samples, consisting of benign prostatic hyperplasia regions and malignant tumors, from 39 prostate cancer patients. Our analysis reveals the convergent effects of distinct copy number alterations impacting on common downstream proteins, which are important for establishing the tumor phenotype. We devise a network-based approach that integrates perturbations across different molecular layers, which identifies a sub-network consisting of nine genes whose joint activity positively correlates with increasingly aggressive tumor phenotypes and is predictive of recurrence-free survival. Further, our data reveal a wide spectrum of intra-patient network effects, ranging from similar to very distinct alterations on different molecular layers. CONCLUSIONS: This study uncovers molecular networks with considerable convergent alterations across tumor sites and patients. It also exposes a diversity of network effects: we could not identify a single sub-network that is perturbed in all high-grade tumor regions.

Inflammatory Myofibroblastic Tumor of the Bladder With FN1-ALK Gene Fusion: Different Response to ALK Inhibition.

Inflammatory myofibroblastic tumors are rare tumors with an ALK (anaplastic lymphoma kinase) gene rearrangement in up to 65% of all cases. In our patient, the tumor was not primary resectable due to its extension. Under neoadjuvant treatment with the first generation ALK inhibitor crizotinib no tumor response was seen, but the following therapy with the next generation ALK inhibitor lorlatinib led to a rapid and deep response, enabling a complete tumor resection by partial cystectomy. Our case indicates that ALK positive inflammatory myofibroblastic tumors which do not respond to ALK inhibition with crizotinib can be successfully treated with newer agents.

Inferring clonal composition from multiple tumor biopsies.

Knowledge about the clonal evolution of a tumor can help to interpret the function of its genetic alterations by identifying initiating events and events that contribute to the selective advantage of proliferative, metastatic, and drug-resistant subclones. Clonal evolution can be reconstructed from estimates of the relative abundance (frequency) of subclone-specific alterations in tumor biopsies, which, in turn, inform on its composition. However, estimating these frequencies is complicated by the high genetic instability that characterizes many cancers. Models for genetic instability suggest that copy number alterations (CNAs) can influence mutation-frequency estimates and thus impede efforts to reconstruct tumor phylogenies. Our analysis suggested that accurate mutation frequency estimates require accounting for CNAs-a challenging endeavour using the genetic profile of a single tumor biopsy. Instead, we propose an optimization algorithm, Chimæra, to account for the effects of CNAs using profiles of multiple biopsies per tumor. Analyses of simulated data and tumor profiles suggested that Chimæra estimates are consistently more accurate than those of previously proposed methods and resulted in improved phylogeny reconstructions and subclone characterizations. Our analyses inferred recurrent initiating mutations in hepatocellular carcinomas, resolved the clonal composition of Wilms' tumors, and characterized the acquisition of mutations in drug-resistant prostate cancers.

Excess Mortality Among Hospitalized Patients With Hypopituitarism-A Population-Based, Matched-Cohort Study.

CONTEXT: Patients with hypopituitarism face excess mortality in the long-term outpatient setting. However, associations of pituitary dysfunction with outcomes in acutely hospitalized patients are lacking. OBJECTIVE: The objective of this work is to assess clinical outcomes of hospitalized patients with hypopituitarism with or without diabetes insipidus (DI). DESIGN, SETTING, AND PATIENTS: In this population-based, matched-cohort study from 2012 to 2017, hospitalized adult patients with a history of hypopituitarism were 1:1 propensity score-matched with a general medical inpatient cohort. MAIN OUTCOME MEASURES: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause readmission rates within 30 days and 1 year, intensive care unit (ICU) admission rates, and length of hospital stay. RESULTS: After matching, 6764 cases were included in the study. In total, 3382 patients had hypopituitarism and of those 807 (24%) suffered from DI. All-cause in-hospital mortality occurred in 198 (5.9%) of patients with hypopituitarism and in 164 (4.9%) of matched controls (odds ratio [OR] 1.32, [95% CI, 1.06-1.65], P = .013). Increased mortality was primarily observed in patients with DI (OR 3.69 [95% CI, 2.44-5.58], P < .001). Patients with hypopituitarism had higher ICU admissions (OR 1.50 [95% CI, 1.30-1.74], P < .001), and faced a 2.4-day prolonged length of hospitalization (95% CI, 1.94-2.95, P < .001) compared to matched controls. Risk of 30-day (OR 1.31 [95% CI, 1.13-1.51], P < .001) and 1-year readmission (OR 1.29 [95% CI, 1.17-1.42], P < .001) was higher among patients with hypopituitarism as compared with medical controls. CONCLUSIONS: Patients with hypopituitarism are highly vulnerable once hospitalized for acute medical conditions with increased risk of mortality and adverse clinical outcomes. This was most pronounced among those with DI.

Risk of Adverse Clinical Outcomes in Hyponatremic Adult Patients Hospitalized for Acute Medical Conditions: A Population-Based Cohort Study.

CONTEXT: Hyponatremia has been associated with excess long-term morbidity and mortality. However, effects during hospitalization are poorly studied. OBJECTIVE: The objective of this work is to examine the association of hyponatremia with the risk of in-hospital mortality, 30-day readmission, and other short-term adverse events among medical inpatients. DESIGN AND SETTING: A population-based cohort study was conducted using a Swiss claims database of medical inpatients from January 2012 to December 2017. PATIENTS: Hyponatremic patients were 1:1 propensity-score matched with normonatremic medical inpatients. MAIN OUTCOME MEASURE: The primary outcome was a composite of all-cause in-hospital mortality and 30-day hospital readmission. Secondary outcomes were intensive care unit (ICU) admission, intubation rate, length-of-hospital stay (LOS), and patient disposition after discharge. RESULTS: After matching, 94 352 patients were included in the cohort. Among 47 176 patients with hyponatremia, 8383 (17.8%) reached the primary outcome compared with 7994 (17.0%) in the matched control group (odds ratio [OR] 1.06 [95% CI, 1.02-1.10], P = .001). Hyponatremic patients were more likely to be admitted to the ICU (OR 1.43 [95% CI, 1.37-1.50], P < .001), faced a 56% increase in prolonged LOS (95% CI, 1.52-1.60, P < .001), and were admitted more often to a postacute care facility (OR 1.38 [95% CI 1.34-1.42, P < .001). Of note, patients with the syndrome of inappropriate antidiuresis (SIAD) had lower in-hospital mortality (OR 0.67 [95% CI, 0.56-0.80], P < .001) as compared with matched normonatremic controls. CONCLUSION: In this study, hyponatremia was associated with increased risk of short-term adverse events, primarily driven by higher readmission rates, which was consistent among all outcomes except for decreased in-hospital mortality in SIAD patients.